There are approximately 1.5 million new cases of head injuries to people in the United States every year. Of these, about 300,000 are severe enough to require hospitalization, and 50,000 to 75,000 will result in a coma that lasts for more than two weeks. Due to constant advances in effective emergency medicine, many patients that sustain a brain injury due to any of a variety of trauma will survive but remain in a severe altered state of consciousness, such as a coma, the deepest state of unconsciousness, or another more emergent but altered state of consciousness, such as persistent vegetative state (PVS) or minimally conscious state (MCS). Such patients fail to emerge to the fully, functional state of awareness of self and environment that they possessed prior to brain injury. Occasionally, some patients may emerge from a particular, deeper state of altered consciousness to a higher state, or even to normal awareness. However, even with emergence to full awareness, it is not uncommon for such individuals to require some form of neurorehabilitation to improve or regain any of a number of neurological functions, such as communication skills, motor skills, memory skills, and various other cognitive functions that permit self care, mobility, and employability. Clearly, patients that are in or have emerged from a severely altered state of consciousness represent a significant emotional, social, and economic burden to their families and to society.
Different therapeutic interventions have been proposed to aid the functional recovery of post-traumatic coma patients, but the results have been inconclusive. There have been a few case reports describing the use of different pharmacological agents on post-traumatic coma patients, e.g., using oral formulations of levodopa and carbidopa (Haig et al., Arch. Phys. Med Rehabil., 71: 1081-1083 (1990)), bromocriptine (Passler et al., Arch. Phys. Med. Rehab., 82: 311-315 (2001)), methylphenidate (Whyte et al., J. Head Trauma Rehabil., 17(4): 284-299 (2002)), and amantidine (Wolf and Gleckman, Brain Injury, 9(5): 487-493 (1995); Meythaler et al., J. Head Trauma Rehabil., 17(1): 300-314 (2002)). The need for innovative clinical research on coma and other altered states of consciousness disorders has never been greater, since relatively recent advances in medicine have enabled survival of a higher percentage of patients of head injury. Yet, there are no generally accepted therapeutic options to promote emergence from an altered state of consciousness or to stimulate neurorehabilitation of patients of brain injuries.
It has been suggested that coma duration is directly related to functional recovery as measured by any of a variety of disability scales used to assess patients, i.e., the longer a patient remains in an altered state of consciousness, the longer the patient requires some form of neurorehabilitative treatment. Such neurorehabilitative treatments may not only have the goal of restoring a patient with brain injury to a higher, preferably normal state of consciousness but also to restore or improve any of a variety of neurological functions that may have been impaired due to the brain injury, such as, communication skills (speaking, writing), cognitive skills (e.g., reasoning, memory), and motor skills (directed movements, walking, running, balancing). In addition, in recent years, important new findings have been made that indicate an ability of the neural network of the brain of a trauma patient to reorganize itself, a mechanism known variously as “neural plasticity”, “axonal plasticity”, “adaptive plasticity”, or “activity-dependent plasticity”, in which interactions between surviving neurons may adopt a new function or be recruited to restore a lost neurological function. A treatment that promotes a patient's emergence to a greater state of awareness should, in theory, also expedite the neurorehabilitation process. Clearly, needs remain for effective therapies to treat impaired neurological function in patients that have suffered brain injury.